Trends in Pharmacological Sciences, Journal Year: 2017, Volume and Issue: 38(11), P. 1016 - 1037
Published: Sept. 19, 2017
Language: Английский
Trends in Pharmacological Sciences, Journal Year: 2017, Volume and Issue: 38(11), P. 1016 - 1037
Published: Sept. 19, 2017
Language: Английский
Annual Review of Neuroscience, Journal Year: 2018, Volume and Issue: 41(1), P. 453 - 473
Published: May 31, 2018
Opioids are the most commonly used and effective analgesic treatments for severe pain, but they have recently come under scrutiny owing to epidemic levels of abuse overdose. These compounds act on endogenous opioid system, which comprises four G protein-coupled receptors (mu, delta, kappa, nociceptin) major peptide families (β-endorphin, enkephalins, dynorphins, nociceptin/orphanin FQ). In this review, we first describe functional organization pharmacology system. We then summarize current knowledge signaling mechanisms by opioids regulate neuronal function neurotransmission. Finally, discuss loci action along peripheral central pain pathways, emphasizing pain-relieving properties against affective dimension experience.
Language: Английский
Citations
375Neuroscience, Journal Year: 2016, Volume and Issue: 338, P. 160 - 182
Published: June 24, 2016
Language: Английский
Citations
344Nature reviews. Neuroscience, Journal Year: 2018, Volume and Issue: 19(8), P. 499 - 514
Published: June 22, 2018
Language: Английский
Citations
307CNS Drugs, Journal Year: 2019, Volume and Issue: 33(10), P. 943 - 955
Published: Oct. 1, 2019
Language: Английский
Citations
245Pharmacological Reviews, Journal Year: 2020, Volume and Issue: 73(1), P. 163 - 201
Published: Dec. 14, 2020
Compulsive drug seeking that is associated with addiction hypothesized to follow a heuristic framework involves three stages (binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation) domains of dysfunction (incentive salience/pathologic habits, negative emotional states, executive function, respectively) via changes in the basal ganglia, extended amygdala/habenula, frontal cortex, respectively. This review focuses on neurochemical/neurocircuitry dysregulations contribute hyperkatifeia, defined as greater intensity emotional/motivational signs symptoms during withdrawal from drugs abuse affect stage cycle. Hyperkatifeia provides an additional source motivation for compulsive reinforcement. Negative reinforcement reflects increase probability response remove aversive stimulus or hyperkatifeia augmented by genetic/epigenetic vulnerability, environmental trauma, psychiatric comorbidity. Neurobiological targets involve neurocircuitry amygdala its connections within-system neuroadaptations dopamine, enkephalin/endorphin opioid peptide, γ-aminobutyric acid/glutamate systems between-system prostress corticotropin-releasing factor, norepinephrine, glucocorticoid, dynorphin, hypocretin, neuroimmune antistress neuropeptide Y, nociceptin, endocannabinoid, oxytocin systems. Such are mediate hedonic set point gradually gains allostatic load shifts homeostatic state state. Based preclinical studies translational date, medications behavioral therapies reset brain stress, antistress, pain return them homeostasis would be promising new medication development.
Language: Английский
Citations
238Neuron, Journal Year: 2019, Volume and Issue: 102(3), P. 529 - 552
Published: May 1, 2019
Language: Английский
Citations
234Frontiers in Pharmacology, Journal Year: 2018, Volume and Issue: 9
Published: Nov. 29, 2018
Opioids are the most effective drugs for treatment of severe pain, but they also cause addiction and overdose deaths, which have led to a worldwide opioid crisis. Therefore, development safer opioids is urgently needed. In this article, we provide critical overview emerging opioid-based strategies aimed at pain relief improved side effect profiles. These approaches comprise biased agonism, targeting (i) receptors in peripheral inflamed tissue (by reducing agonist access brain, use nanocarriers, or low pH-sensitive agonists); (ii) heteromers multiple monovalent, bivalent, multifunctional ligands); (iii) receptor splice variants; (iv) endogenous peptides preventing their degradation enhancing production by gene transfer). Substantial advancements underscored pharmaceutical new such as κ-receptor agonists, treatments augmenting action opioids, entered clinical trials. Additionally, there several promising novel comprehensively examined preclinical studies, might require careful rethinking.
Language: Английский
Citations
156Molecular Pharmacology, Journal Year: 2020, Volume and Issue: 98(2), P. 96 - 108
Published: June 2, 2020
In the mid-1970s, an intense race to identify endogenous substances that activated same receptors as opiates resulted in identification of first opioid peptides. Since then, >20 peptides with receptor activity have been discovered, all which are generated from three precursors, proenkephalin, prodynorphin, and proopiomelanocortin, by sequential proteolytic processing prohormone convertases carboxypeptidase E. Each these binds types (μ, δ, or κ), albeit differing affinities. Peptides derived proenkephalin prodynorphin broadly distributed brain, mRNA encoding precursors highly expressed some peripheral tissues. Various approaches used explore functions specific behaviors brain circuits. These methods include directly administering ex vivo (i.e., excised tissue) (in animals), using antagonists infer peptide activity, genetic knockout precursors. Collectively, studies add our current understanding function opioids, especially when similar results found different approaches. We briefly review history peptides, highlight major findings, address several myths widely accepted but not supported recent data, discuss unanswered questions future directions for research.
Language: Английский
Citations
122Science Translational Medicine, Journal Year: 2018, Volume and Issue: 10(456)
Published: Aug. 29, 2018
The small-molecule AT-121 is an agonist of nociceptin and mu opioid peptide receptors mediates analgesia without opioid-associated side effects in nonhuman primates.
Language: Английский
Citations
115Cell, Journal Year: 2019, Volume and Issue: 178(3), P. 653 - 671.e19
Published: July 1, 2019
Language: Английский
Citations
112